Circ_0060055 Promotes the Growth, Invasion, and Radioresistance of Glioblastoma by Targeting MiR-197-3p/API5 Axis.

Abstract

Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression. Our study aims to reveal the role of circ_0060055 in the progression of glioblastoma (GBM) and its potential molecular mechanism. The expression of circ_0060055, microRNA (miR)-197-3p, and apoptosis inhibitor 5 (API5) was determined by quantitative real-time PCR. GBM cell proliferation, apoptosis, and invasion were assessed using cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry, and transwell assay. Besides, the radiosensitivity of cells also was assessed using colony formation assay. The interaction between miR-197-3p and circ_0060055 or API5 was analyzed by dual-luciferase reporter assay and RNA pull-down assay. Animal experiments were conducted to measure the effect of circ_0060055 on GBM tumor growth and radiosensitivity in vivo. Circ_0060055 was overexpressed in GBM tumor tissues and cells, and its silencing suppressed GBM cell proliferation and invasion, while promoted apoptosis and radiosensitivity. In terms of mechanism, circ_0060055 could interact with miR-197-3p, and miR-197-3p could target API5. API5 expression also could be positively regulated by circ_0060055. Function experiments suggested that miR-197-3p inhibitor abolished the effect of circ_0060055 knockdown on GBM cell growth, invasion, and radiosensitivity. MiR-197-3p repressed GBM cell progression and improved radiosensitivity, and this effect was eliminated by API5 upregulation. In vivo experiments confirmed that circ_0060055 knockdown reduced GBM tumor growth and enhanced the radiosensitivity of tumors. This study revealed that circ_0060055 contributed to GBM progression and radioresistance through miR-197-3p/API5 pathway, providing a potential target for GBM treatment.